This grant was begun in October, 1974, with a series of experiments designed to show synergism between combination immunosuppressive drug therapy in the prolongation of renal allografts in the dogs. The host was to be monitored using the mixed lymphocyte culture reaction (MLR). It was initially shown and confirmed that synergism between azathioprine and cytoxan did exist when methylprednisolone was given. However, uniform prolongation overlong periods of time could not be achieved and monitoring this combination of therapy using MLR proved to be unreliable. Hence, our studies took to new approaches. Firstly, to develop a more specific test to monitor the effectiveness of immunosuppressive therapy. Hence, we developed the mixed-kidney lymphocyte culture reaction (MKLC). This technique was evolved by showing that the addition of small quantities of 2-mercaptoethanol to the culture media allowed reproducible results. In an attempt to achieve greater kidney graft survival, a new drug MGA which prolonged heart allografts in rats, is now being studied for its ability to prolong kidney allografts in dogs and for its ability to produce synergism with azathioprine and cytoxan.